Imaging thrombi with radiolabelled anti-fibrin monoclonal antibodies

Abstract

Monoclonal antibodies which recognize fibrin but not fibrinogen can be used to detect deposits of fibrin in vivo. Recently, two monoclonal antibodies with such specificity have been created: 59D8 (raised against a synthetic heptapeptide by Hui et al.) and T2G1s (raised against a fibrin fragment by Kudryk et al.). These two antibodies appear to share the same epitope in the N-terminus of the beta chain of fibrin, a site which is not exposed in fibrinogen. In the form of radioiodinated IgG, both antibodies have been shown to bind to deposits of fibrin and induce fresh thrombi in animal models. Use of antibody fragments which retain immunoreactivity could enhance thrombus detection by (1) increasing the rate of blood disappearance and thus increasing target/background contrast, and (2) favouring renal excretion over liver uptake. Antibody fragments which have been derivatized to contain diethylenetriaminepropyleneamineoxime (DTPA) groups have been labelled with 111In and used to produce images of fresh thrombi in animal models with thrombus-to-blood ratios of greater than 7:1 and thrombus-to-muscle ratios of greater than 200:1 by 24 h post injection. Initial clinical trials of these antibodies suggest that thrombi may be visualized within the first few hours after injection, although the image quality improves with time. Shorter-lived radiolabels (such as 99Tcm) may be useful for anti-fibrin antibody fragments if adequate thrombus/background contrast can be achieved within a few hours post injection.